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101.
102.
Background
Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood.This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation.Methods
Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand.Results
MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P < 0.01). TIMP-1 levels decreased from 3.5 μg/g [0.6 to 7.8] to 1.5 μg/g [0.3 to 4.9] (P = 0.16). MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05). Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05). Macrophage numbers remained level. MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01).Conclusion
During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline. 相似文献103.
TE Willnow C Antignac AW Br?ndli EI Christensen RD Cox D Davidson JA Davies O Devuyst G Eichele ND Hastie PJ Verroust A Schedl IC Meij 《Organogenesis》2005,2(2):42-47
Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics 相似文献
104.
In order to reconstruct phylogenetic trees from extremely dissimilar
sequences it is necessary to estimate accurately the extent of sequence
divergence. In this paper a new method of sequence analysis, Markov triple
analysis, is developed for determining the relative frequencies of
nucleotide substitutions within the three branches of a three-taxon
dendrogram. Assuming that nucleotide sites are independently and
identically distributed and assuming a Markov model for nucleotide (or
protein) evolution, it is shown that the unique Markov matrices can be
reconstructed given only the joint probability distribution relating three
taxa. (In the much simpler case involving only two taxa and two character
states, Markov matrices can also be reconstructed, provided symmetry
assumptions are placed on the elements of the matrices.) The method is
illustrated using sequence data from the combined first and second codon
positions derived from complete human, mouse, and cow mitochondrial
sequences.
相似文献
105.
DNA hybridization evidence for the principal lineages of hummingbirds (Aves:Trochilidae) 总被引:3,自引:0,他引:3
The spectacular evolutionary radiation of hummingbirds (Trochilidae) has
served as a model system for many biological studies. To begin to provide a
historical context for these investigations, we generated a complete matrix
of DNA hybridization distances among 26 hummingbirds and an outgroup swift
(Chaetura pelagica) to determine the principal hummingbird lineages. FITCH
topologies estimated from symmetrized delta TmH-C values and subjected to
various validation methods (bootstrapping, weighted jackknifing, branch
length significance) indicated a fundamental split between hermit
(Eutoxeres aquila, Threnetes ruckeri; Phaethornithinae) and nonhermit
(Trochilinae) hummingbirds, and provided strong support for six principal
nonhermit clades with the following branching order: (1) a predominantly
lowland group comprising caribs (Eulampis holosericeus) and relatives
(Androdon aequatorialis and Heliothryx barroti) with violet-ears (Colibri
coruscans) and relatives (Doryfera ludovicae); (2) an Andean-associated
clade of highly polytypic taxa (Eriocnemis, Heliodoxa, and Coeligena); (3)
a second endemic Andean clade (Oreotrochilus chimborazo, Aglaiocercus
coelestis, and Lesbia victoriae) paired with thorntails (Popelairia
conversii); (4) emeralds and relatives (Chlorostilbon mellisugus, Amazilia
tzacatl, Thalurania colombica, Orthorhyncus cristatus and Campylopterus
villaviscensio); (5) mountain-gems (Lampornis clemenciae and Eugenes
fulgens); and (6) tiny bee-like forms (Archilochus colubris, Myrtis fanny,
Acestrura mulsant, and Philodice mitchellii). Corresponding analyses on a
matrix of unsymmetrized delta values gave similar support for these
relationships except that the branching order of the two Andean clades (2,
3 above) was unresolved. In general, subsidiary relationships were
consistent and well supported by both matrices, sometimes revealing
surprising associations between forms that differ dramatically in plumage
and bill morphology. Our results also reveal some basic aspects of
hummingbird ecologic and morphologic evolution. For example, most of the
diverse endemic Andean assemblage apparently comprises two genetically
divergent clades, whereas the majority of North American hummingbirds
belong a single third clade. Genetic distances separating some
morphologically distinct genera (Oreotrochilus, Aglaiocercus, Lesbia;
Myrtis, Acestrura, Philodice) were no greater than among congeneric
(Coeligena) species, indicating that, in hummingbirds, morphological
divergence does not necessarily reflect level of genetic divergence.
相似文献
106.
107.
108.
Despite their remoteness from sources of atmospheric pollutant emissions, the Afromontane tarns in the Maloti-Drakensberg region are perfect candidates to study the negative effects of acidifying atmospheric pollution, because mountain lakes are widely recognised as sentinel ecosystems, unimpacted by direct human disturbance within their catchments. Thirty-four tarns were sampled in the Maloti-Drakensberg region and most were found to be extremely sensitive to acidic deposition, as indicated by their low acid neutralising capacity. There are very few studies of freshwater critical loads for any region within South Africa. The steady-state water chemistry model (SSWC) was adapted and used to determine critical loads, whereas exceedance was estimated relative to modelled regional deposition data, in order to understand the risk of harmful effects to aquatic ecosystems. Seventy-six percent of sampled sites across the Maloti-Drakensberg would exceed critical loads even at the lowest modelled deposition levels, but there are no current measured deposition data for the region. The sensitivity of the Maloti-Drakensberg tarns needs to be considered in future policy formulation regarding acceptable levels of acidifying atmospheric pollution from South Africa’s energy sector and indicates the need for assessing aquatic ecosystem impacts in other regions of South Africa. 相似文献
109.
110.
N Dragon N G Seidah M Lis R Routhier M Chrétien 《Canadian journal of biochemistry》1977,55(6):666-670
The complete amino acid sequence of human beta-endorphin was obtained by automatic sequencing of a sulfonyl isothiocyanate derivative of this peptide, in combination with peptide mapping of a tryptic digest of the native molecule. It was found to be identical with the carboxy-terminal portion 61-91 of human beta-lipotropin (beta-LPH). The morphine-like activity of beta-endorphin is comparable both in the mouse vas deferens bioassay and in the opiate receptor binding assay. However, beta-LPH is not active up to concentrations of 10(-6) M. 相似文献